Electronic breath actuated droplet delivery systems with dose metering capabilities, inhalation topography methods, and related methods of use

ABSTRACT

Methods, devices and systems are provided wherein compositions are delivered to the pulmonary system of an intended user via inhalation in a controlled manner and at a desired doses and/or amounts, e.g., within a desired dosage window and/or inhalation topography. In certain embodiments, dosage windows and/or inhalation topography may be used, e.g., to provide for controlled cessation of use or to provide a desired therapeutic window.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 U.S.C. § 119(e) to U.S. PatentApplication No. 62/796,561, filed Jan. 24, 2019 entitled “ELECTRONICBREATH ACTUATED DROPLET DELIVERY DEVICE WITH DOSE METERING CAPABILITIESAND METHODS OF USE,” U.S. Patent Application No. 62/803,196, filed Feb.8, 2019, 2019 entitled “ELECTRONIC BREATH ACTUATED DROPLET DELIVERYDEVICE WITH DOSE METERING CAPABILITIES AND METHODS OF USE,” U.S. PatentApplication No. 62/823,335, filed Mar. 25, 2019 entitled “ELECTRONICBREATH ACTUATED DROPLET DELIVERY DEVICE WITH DOSE METERING CAPABILITIESAND METHODS OF USE,” U.S. Patent Application No. 62/860,086, filed Jun.11, 2019 entitled “ELECTRONIC BREATH ACTUATED DROPLET DELIVERY DEVICEWITH DOSE METERING CAPABILITIES, INHALATION TOPOGRAPHY METHODS ANDRELATED METHODS OF USE,” and U.S. Patent Application No. 62/906,652,filed Sep. 26, 2019 entitled “ELECTRONIC BREATH ACTUATED DROPLETDELIVERY DEVICE WITH DOSE METERING CAPABILITIES, INHALATION TOPOGRAPHYMETHODS AND RELATED METHODS OF USE,” the entire contents of which areincorporated herein by reference in their entireties for all purposes.

FIELD OF THE INVENTION

This disclosure relates to droplet delivery systems and related methodsand more specifically to droplet delivery systems and with dose meteringcapabilities and related methods for the delivery of fluids to thepulmonary system.

BACKGROUND OF THE INVENTION

The use of aerosol generating devices for the delivery of substances tothe pulmonary system is an area of large interest. A major challenge isproviding a device that delivers an accurate, consistent, and verifiabledose, with a droplet size that is suitable for successful delivery ofsubstances to the targeted areas of the pulmonary system.

Dose verification, delivery and inhalation of the correct amount atdesired times are also important. Problems emerge when users misuse orincorrectly administer material from inhalers and delivery devices.

Accordingly, there is a need for inhalation devices that deliverdroplets of a suitable size range, with a dose that is controllable andverifiable, and provides feedback regarding correct and consistent usageof the device.

SUMMARY OF THE INVENTION

In one aspect of the disclosure, a method for controlling the doseand/or amount of a composition for delivery to the pulmonary system of auser via inhalation is provided. The method generally comprisesreceiving, at a computing system based on user input, a request for adesired dose or amount of at least one agent or ingredient of acomposition for delivery to the pulmonary system of a user viainhalation; at the computing system and in response to receiving therequest, determining inhalation delivery device operating parameters toprovide the requested desired dose or amount of at least one agent oringredient of a composition for delivery to the pulmonary system of auser via inhalation; generating, at the computing system, instructionsfor activation and operation of an inhalation delivery device to providethe requested desired dose or amount based on the determined inhalationdelivery device operating parameters; and transmitting the instructionsfrom the computing system to an ejector mechanism of an inhalationdelivery device for execution at the inhalation delivery device toprovide for activation and operation of the inhalation delivery deviceupon use to thereby control the dose and/or amount of the at least oneagent or ingredient of a composition for delivery to the pulmonarysystem of user via inhalation.

In certain embodiments, the request for a desired dose or amountcomprises an inhalation topography to achieve a desired dosing regimen.The inhalation topography may facilitate cessation of use. In someembodiments, the inhalation topography may gradually reduce the dose oramount over time to thereby facilitate cessation of use. In otherembodiments, the inhalation topography may include an initial bolus doseat an initial loading dose, followed by maintenance doses at reduceddose.

In certain embodiments, the request includes independently selecteddoses and/or amounts at least two agents or ingredients such thatinstructions are provided to the inhalation delivery device toindependently control the dose and/or amount of each of said at leasttwo agents or ingredients separately.

In other embodiments, the composition may comprise nicotine, and themethod may comprise controlling the dose or amount of nicotine fordelivery to the pulmonary system of a user via inhalation. In certainembodiments, the composition may further comprise a flavoring, and therequest may include independently selected doses and/or amounts fornicotine and the flavoring such that instructions are provided to theinhalation delivery device to independently control the dose and/oramount of each of nicotine and the flavoring separately.

In some embodiments, the computing system may be a user computingdevice, and the user input is received via a user interface of the usercomputing device. In other embodiments, an inhalation delivery devicecomprises the computing system, and the user input is received via auser interface of the inhalation delivery device, via input from userinhalation flowrates, or a combination thereof. The user interface ofthe inhalation delivery device may comprise user input buttons, an LCDtouchscreen, or combinations thereof.

In other aspects, a computing system is provided. The computer systemcomprises one or more processors; and a memory storing instructionsexecutable by the one or more processors, wherein, when executed by theone or more processors, the instructions cause the one or moreprocessors to perform the method for controlling the dose and/or amountof a composition for delivery to the pulmonary system of a user viainhalation.

In certain embodiments, the method comprises receiving, based on userinput, a request for a desired dose or amount of at least one agent oringredient of a composition for delivery to the pulmonary system of auser via inhalation; determining inhalation delivery device operatingparameters to provide the requested desired dose or amount of at leastone agent or ingredient of a composition for delivery to the pulmonarysystem of a user via inhalation; generating instructions for activationand operation of an inhalation delivery device to provide the requesteddesired dose or amount based on the determined inhalation deliverydevice operating parameters; and transmitting the instructions to anejector mechanism of an inhalation delivery device for execution at theinhalation delivery device to provide for activation and operation ofthe inhalation delivery device upon use to thereby control the doseand/or amount of the at least one agent or ingredient of a compositionfor delivery to the pulmonary system of user via inhalation.

In yet other aspects, a method of displaying historical data of use ofan inhalation delivery device is provided. The method generallycomprises receiving, at a user computing device from a user interface, arequest for historical data associated with use of an inhalationdelivery device to deliver an inhaled composition, the historical datacomprising an element selected from: number of doses administered,dosages and amounts administered, average inhalation topography, andcombinations thereof transmitting, from the user computing device to aninhalation delivery device, the request for historical data; receiving,at the user computing device from the inhalation delivery device, therequested historical data; generating, at the user computing device,graphical data for rendering and displaying a report of the requestedhistorical data; rendering the graphical data, at the user computingdevice; and displaying a report on a display of the user computingdevice, the report including graphical elements including the historicaldata.

In certain embodiments, the displaying of historical data of use of aninhalation delivery device facilities the cessation of use. Therendering of the graphical data may further include displaying changesin dosage amounts over time to illustrate reductions or increases in useof the inhalation delivery device.

In other embodiments, the method further comprises receiving a selectionof a graphical element of the report at the user computing device;generating, in response to receiving the selection, additional graphicaldata related to the selected graphical element; rendering the additionalgraphical data, at the user computing device; and displaying a report ona display of the user computing device, the report including additionalgraphical data related to the selected graphical element. In certainembodiments, the report comprises education information related tocessation of use.

While multiple embodiments are disclosed, still other embodiments of thepresent disclosure will become apparent to those skilled in the art fromthe following detailed description, which shows and describesillustrative embodiments of the disclosure. As will be realized, theinvention is capable of modifications in various aspects, all withoutdeparting from the spirit and scope of the present disclosure.Accordingly, the detailed descriptions are to be regarded asillustrative in nature and not restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram illustrating an example lab result processingsystem, according to one embodiment of the disclosure.

FIGS. 2A-2B are exemplary user interfaces that may be provided through adosage and topography management system, as illustrated in FIG. 1.

FIG. 3 is a flow chart illustrating a method for controlling the doseand/or amount of a composition for delivery to the pulmonary system of auser via inhalation, according to one embodiment of the disclosure.

FIGS. 4A-4G illustrate exemplary inhalation topographies, in accordancewith embodiments of the disclosure. FIG. 4A illustrates a linearrelationship wherein no dosing occurs prior to a minimum thresholdinhalation flow rate. FIG. 4B illustrates a non-linear relationship withan optimum inhalation range to facilitate delivery to the pulmonarysystem. FIG. 4C illustrates a linear relationship wherein no dosingoccurs prior to a minimum threshold inhalation flow rate along with aminimum dose rate. FIG. 4C illustrates a similar linear relationshipwherein no dosing occurs prior to a minimum threshold inhalation flowrate along, with both a minimum and a maximum dose rate. FIG. 4Eillustrates a non-linear relationship that escalates dose rate morequickly with inhalation rate. FIG. 4F illustrates a non-linearrelationship that escalates dose rate more slowly with inhalation rate.FIG. 4G illustrates a step-wise increase in dose rate with inhalationrate.

FIGS. 5A-5B illustrate the use of micro-strops in ejection activation toachieve desired dosing rates, in accordance with embodiments of thedisclosure. FIG. 5A illustrates a 30% dose rate, while FIG. 5Billustrates an 80% dose rate.

FIG. 6 is a flow chart illustrating a method for requesting anddisplaying graphical data, according to one embodiment of thedisclosure.

FIG. 7 is a diagram illustrating an example of a computing system whichmay be used in implementing embodiments of the present disclosure.

The foregoing and other objects, features, and advantages of the presentdisclosure set forth herein will be apparent from the followingdescription of particular embodiments of those inventive concepts, asillustrated in the accompanying drawings. Also, in the drawings the likereference characters refer to the same parts throughout the differentviews. The drawings depict only typical embodiments of the presentdisclosure and, therefore, are not to be considered limiting in scope.

DETAILED DESCRIPTION

To address these and other needs, methods, devices and systems areprovided wherein compositions are delivered to the pulmonary system ofan intended user via inhalation in a controlled manner and at a desireddoses and/or amounts. In certain aspects, the methods, devices andsystems deliver inhaled compositions in a manner so as to preventmisuse, to prevent overuse, to provide controlled cessation of use, orto provide other desired dosage and/or amount control or metering by theintended user or other third parties.

In certain aspects, the methods, devices and systems can improve humanhealth through more effective use of inhaled compositions, includingprescription drugs for Asthma/COPD and oncology; cannabis agents,including therapeutic medical marijuana; and nicotine agents. In certainembodiments, the methods, devices and systems provide for the deliveryof inhaled compositions with reduced side effects, while allowing forcontrolled dosing and administration such that users may have improvedcontrol of use and inhalation topography. In certain embodiments, suchimproved control of use and inhalation topography may facilitatecessation efforts of various inhaled compositions, e.g., nicotine,controlled substances, etc.

In certain aspects, the methods, devices and systems allow for deliveryof compositions to the pulmonary system of an intended user viainhalation at controlled dosages and/or amounts, e.g., within a desireddosage window and/or inhalation topography. In certain embodiments, themethods, devices and systems achieve a desired dosage or amount deliveryvia controlled dosage or amount metering. In certain embodiments, dosagewindows and/or inhalation topography may be used, e.g., to provide forcontrolled cessation of use or to provide a desired therapeutic window.

Without being limited, in certain aspects, dosage and/or amount meteringmay provide a desired inhalation topography. As used herein, inhalationtopography refers to the relationship between inhalation flow rate anddose/amount administered. The inhalation topography may be any desiredrelationship, e.g., zero order (i.e., no change in dose/amountadministered with change in flow rate, once a minimum threshold flowrate is achieved); linear, non-linear, etc. In certain embodiments, adesired dosing regimen may also require more than one inhalationtopography, selected based on the particular dose to be administered(e.g., initial dose, maintenance dose, morning dose, evening dose,add-on dose, “stress use” dose, etc.)

By way of non-limiting example, in certain embodiments, the inhalationtopography may include an initial bolus dose and/or amount followed bymaintenance dosing and/or amounts, so as to maintain a desiredtherapeutic dosage window or to provide controlled cessation of use. Inother embodiments, the inhalation topography may include variations indose/amount administration rate based on the time of day or trigger foruse (e.g., morning use, day time use, night time use, “stress use”,etc.). As explained in further detail herein, the methods, devices andsystems of the disclosure uniquely allow for dosage and/or amountmetering in a controlled manner so as to prevent misuse, to preventoveruse, to provide controlled cessation of use, or to provide otherdesired dosage and/or amount control or metering by the intended user orother third parties.

As will be recognized by those of skill in the art, desired dosing oradministration, including desired therapeutic windows, will depend onthe composition to be delivered and attributes of the intended user,including age, weight, sex, health, etc. By way of non-limiting example,dosing or administration may be based on a μg of agent/kg of subjectweight basis, and may be refined based on the particularpharmacokinetics of the intended subject if desired.

In connection with the methods, devices, and systems discussed herein,inhalation delivery devices and systems are disclosed, which are capableof delivering a defined inhalation volume such that an adequate andrepeatable high percentage of the droplets are delivered into thedesired location within the airways, e.g., the mouth, throat, and/oralveolar airways, etc., of the subject during use. The inhalationdelivery device and systems overcome limitations of the currentlyavailable inhalation devices and vapes, in part, by providing formetering of dosing and providing for desired inhalation topography anddosing regimens.

In certain embodiments, the methods, devices and systems of thedisclosure may be used to deliver any suitable composition comprisingone or more active agent or combination of active agents to thepulmonary system of a user. As generally understood, an active agent isany compound or substance that may exert a biological effect on a userwhen administered to the user. In the context of the present disclosure,such administration is via inhalation.

In certain aspects of the disclosure, the compositions to beadministered may comprise one or more active agents in combination withone or more additives, flavorings or other excipients, formulatedtogether as a single composition or as separate compositions forcombination upon administration. As described in further detail herein,the methods, devices and systems of the disclosure may be used toprovide for dosage and/or amount control and metering of the compositionas a whole, of an one or more active agents, of one or more additives,flavorings, or other excipients, wherein the metering is simultaneouscontrolled for the entire composition, independently controlled byingredient, or any desired allocation of control of dosage and/or amountof ingredient and combination thereof.

For example, the methods, devices and systems may be used to deliverycompositions including therapeutic agents, such as small and largemolecules. In certain embodiments, the methods, devices, and systems ofthe disclosure may be used to deliver compositions including activeagents with a potential for abuse or overdose, such as nicotine andsalts thereof, opioid analgesics, psycho-stimulants, cannabinoidagonists, dopamine agonists, steroids, and sedative hypnotics to thepulmonary system of an intended user via inhalation in a controlledmanner which is only enabled by instructions from a doctor or pharmacy.In certain embodiments, the compositions may comprise additives,flavorings and other excipients, as desired. Again, such additives,flavoring, and other excipients may be formulated together with theactive agent(s) as a single composition, or as separate compositions forcombination upon administration.

In some embodiments, the methods, devices, and systems of the disclosuremay be used to deliver a composition comprising nicotine or a saltthereof, e.g., including the water-nicotine azeotrope. By way ofnon-limiting example, the nicotine or salt thereof may be the naturallyoccurring alkaloid compound having the chemical nameS-3-(1-methyl-2-pyrrolidinyl)pyridine, which may be isolated andpurified from nature or synthetically produced in any manner, or any ofits occurring salts containing pharmacologically acceptable anions, suchas hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate orbisulfate, phosphate or acid phosphate, acetate, lactate, citrate oracid citrate, tartrate or bitartrate, succinate, maleate, fumarate,gluconate, pyruvate, saccharate, benzoate, methanesulfonate,ethanesulfonate, benzenesulfonate, p-toluene sulfonate, camphorate andpamoate salts. In other embodiments, the composition may further includeany pharmacologically acceptable derivative, metabolite or analog ofnicotine which exhibits pharmacotherapeutic properties similar tonicotine. Such derivatives and metabolites are known in the art, andinclude cotinine, norcotinine, nornicotine, nicotine N-oxide, cotinineN-oxide, 3-hydroxycotinine and 5-hydroxycotinine or pharmaceuticallyacceptable salts thereof.

In certain embodiments, the methods, devices, and systems of thedisclosure may be used to deliver a composition comprising one or moreactive agents that may isolated or derived from cannabis. For instance,the agent may be a natural or synthetic cannabinoid, e.g., THC(tetrahydrocannabinol), THCA (tetrahydrocannabinolic acid), CBD(cannabidiol), CBDA (cannabidiolic acid), CBN (cannabinol), CBG(cannabigerol), CBC (cannabichromene), CBL (cannabicyclol), CBV(cannabivarin), THCV (tetrahydrocannabivarin), CBDV (cannabidivarin),CBCV (cannabichromevarin), CBGV (cannabigerovarin), CBGM (cannabigerolmonomethyl ether), CBE (cannabielsoin), CBT (cannabicitran), and variouscombinations thereof. In other embodiments, the agent may be a ligandthat bind the cannabinoid receptor type 1 (CB1), the cannabinoidreceptor type 2 (CB2), or combinations thereof. In particularembodiments, the agent may comprise THC, CBD, or combinations thereof.By way of example, the agent may comprise 95% THC, 98% THC, 99% THC, 95%CBD, 98% CBD, 99% CBD, etc.

In certain aspects, the methods, devices and systems of the disclosuremay be used to deliver compositions including one or more active agentshaving the potential for abuse, e.g., including opioid analgesics,psycho-stimulants, cannabinoid agonists, dopamine agonists, steroids,and sedative hypnotics. By way of non-limiting example, opioidanalgesics include, but are not limited to, morphine, heroin,hydromorphone, oxymorphone, buprenorphine, levorphanol, butorphanol,codeine, dihydrocodeine, hydrocodone, oxycodone, meperidine, methadone,nalbulphine, opium, pentazocine, propoxyphene, as well as less widelyemployed compounds such as alfentanil, allylprodine, alphaprodine,anileridine, benzylmorphine, bezitramide, clonitazene, cyclazocine,desomorphine, dextromoramide, dezocine, diampromide, dihydromorphine,dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate,dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene,ethylmorphine, etonitazene, fentanyl, hydroxypethidine, isomethadone,ketobemidone, levallorphan, levophenacylmorphan, lofentanil, meptazinol,metazocine, metopon, myrophine, narceine, nicomorphine, norpipanone,papvretum, phenadoxone, phenomorphan, phenazocine, phenoperidine,piminodine, propiram, sufentanil, tramadol, tilidine, and salts andmixtures thereof.

In other embodiments, the methods, devices and systems of the disclosuremay be used to treat various diseases, disorders and conditions bydelivering therapeutic agents to the pulmonary system of a subject. Inthis regard, the methods, devices and systems may be used to delivertherapeutic agents both locally to the pulmonary system, andsystemically to the body. In certain embodiments, the therapeutic agentmay include THC, CBD, or other cannabinoids for the treatment ofepilepsy, seizures and other conditions.

In accordance with certain aspects of the disclosure, controlled dosagesto achieve a desired inhalation topography or therapeutic dosage windowmay vary depending on the particular composition and therapeutic agentdelivered to an intended user, and will also vary according to the age,body weight, and response of the individual user.

Suitable dosing regimens can be selected by those skilled in the artwith due consideration of such factors. In general, daily dosages mayrange of from about 1 μg/kg to about 150 mg/kg per day. In certainlyembodiments, a daily dose range may range from about 5 μg/kg to about100 mg/kg per day, from about 8 μg/kg to about 90 mg/kg per day, fromabout 8 μg/kg to about 10 mg/kg per day, etc. In selecting desireddosing regimens and inhalation topography, dosing may be initiated at alower dose, and increased if necessary, as either a single dose ordivided doses, depending on the user's global response. Alternatively,in some instance, it may be desired to administer a larger initial bolusdose, followed by smaller maintenance doses. It may be necessary to usedosages of the composition outside the ranges disclosed herein in somecases, as will be apparent to those of ordinary skill in the art.Furthermore, it is noted that the skilled artisan will know how and whento interrupt, adjust, or terminate dosing in conjunction with individualuser response.

By way of non-limiting example, the devices and systems of thedisclosure may be configured to provide dose and/or amount metering atdesired increments, e.g., 5 microgram, 10 microgram, 15 microgram, 20microgram, 25 microgram, 30 microgram, 35 microgram, 40 microgram, 45microgram, 50 microgram, etc. increments, to achieve a desired doseand/or amount. For instance, such incremental dosing may be used toachieve a desired dosage of, e.g., 1-1000, 10-500, 20-100, etc.microgram doses (e.g., at 10 microgram increments) per inhalation. Asexplained in further detail herein, the devices and systems of thedisclosure may provide the desired dosing increments through actuationof an ejector mechanism for a designated duration of time.

In one embodiment, compositions may be administered as a singleonce-a-day dose. In another embodiment, compositions may be administeredas divided doses throughout a day. As will be apparent, the methods,devices and systems of the disclosure provide for an efficient mechanismfor providing administration of divided doses throughout the day in acontrolled manner, e.g., to provide desired dosages and/or inhalationtopography.

Certain aspects of the disclosure relate to a system for delivery ofinhaled compositions to the pulmonary system of a user. In someembodiments, the system may include one or more inhalation deliverydevices with dose metering capabilities, which may optionally interfacewith or communicate with one or more computing devices (e.g., wirelesscommunication device, server, personal computer, etc.). In someembodiments, the systems of the disclosure include one or moreinhalation delivery devices and one or more communication devices,wherein one or more of the inhalation delivery devices are interfacedwith, or in communication with one or more of the computing devices. Thesystems of the disclosure provide substantial improvements over currentinhaled delivery systems by improving dosing precision, dosingreliability, and delivery to the user. In certain embodiments, thesystems of the disclosure include fully integrated monitoringcapabilities designed to enhance dose metering and compliance.

In certain embodiments, the devices and systems may be configured todeliver droplets to various sites within the pulmonary system of theuser, e.g., the mouth, throat, alveolar airways, etc. By way of example,for deposition in alveolar airways, droplets with aerodynamic diametersin the ranges of 1 to 6 μm are optimal, with droplets below about 4 μmshown to more effectively reach the alveolar region of the lungs, whilelarger droplets above about 6 μm are deposited in the mouth, on thetongue, or strike the throat and coat the bronchial passages. Smallerdroplets, for example less than about 1 μm that penetrate more deeplyinto the lungs have a tendency to be exhaled. However, for certainagents and uses, droplets smaller than 1 μm for quick adsorption in thedeep lung may be desirable, e.g., it may be desired to utilize dropletsless than 4 μm, less than 2 μm, and less than 1 μm for the delivery ofnicotine and related substances to the deep lungs.

In certain embodiments, the devices and systems may be configured todeliver droplets in a controllable and defined droplet size range. Byway of example, the droplet size range includes at least about 50%, atleast about 60%, at least about 70%, at least about 85%, at least about90%, between about 50% and about 90%, between about 60% and about 90%,between about 70% and about 90%, etc., of the ejected droplets are inthe respirable range of below about 4 μm, below about 3 μm, below about2.5 μm, below about 2 μm, between about 0.7 μm and about 4 μm, betweenabout 0.7 μm and about 3 μm, between about 0.7 μm and about 2.5 μm,between about 0.7 μm and about 2.0 μm, between about 0.7 μm and about1.5 μm, between about 0.7 μm and about 1.0 μm, etc.

Certain embodiments of the disclosure may be configured to targetmultiple sites within the pulmonary system of user, e.g., the mouth(including the tongue) and the alveolar airways, as described in furtherdetail herein. As explained in further detail herein, the devices andsystems of the disclosure may deliver droplets to specific sites withinthe pulmonary system through the ejection of droplets of controlleddroplet size(s).

In other embodiments, the devices and systems may be configured todeliver droplets having one or more diameters, relative to one another,such that droplets having multiple diameters relative to one anothertarget multiple regions in the airways (mouth, tongue, throat, upperairways, lower airways, deep lung, etc.) By way of example, dropletdiameters may range from about 0.7 μm to about 200 μm, about 0.7 μm toabout 100 μm, about 0.7 μm to about 60 μm, about 0.7 μm to about 40 μm,about 0.7 μm to about 20 μm, about 0.7 μm to about 5 μm, about 0.7 μm toabout 4.7 μm, about 0.7 μm to about 4 μm, about 0.7 μm to about 3.0 μm,about 0.7 μm to about 2.5 μm, about 0.7 μm and about 2.0 μm, about 0.7μm and about 1.5 μm, about 0.7 μm and about 1.0 μm-about 5 μm to about20 μm, about 5 μm to about 10 μm, and combinations thereof. Inparticular embodiments, at least a fraction of the droplets havediameters in the respirable range, while other droplets may havediameters in other sizes so as to target non-respirable locations (e.g.,larger than about 5 μm). Illustrative ejected droplet streams in thisregard might have 50%-70% of droplets in the respirable range (less thanabout 5 μm), and 30%-50% outside of the respirable range (about 5μm-about 10 μm, about 5 μm-about 20 μm, etc.)

In other aspects of the disclosure, methods for generating an ejectedstream of droplets for delivery to the pulmonary system of user usingthe devices and systems of the disclosure are provided.

As explained in further detail herein, in certain embodiments, theinhalation delivery devices of the disclosure may include a housing, oneor more fluid reservoirs, one or more droplet ejector mechanisms, and acontroller having a processor that may be programmed to provide thedesired dosing increments. For instance, the processor may activate theejector mechanism for a designated duration so as to eject droplets toachieve a desired dosing increment. The processor may be programmed inany suitable manner. In certain embodiments, the processor may beprogrammed by “reading” instructions from other device components (asexplained in further detail herein); the microprocessor may be hardprogrammed at the factory, pharmacy or doctor's office; the processormay be programmed via a wireless interface from an external device(e.g., a smart device or other portable wireless device); themicroprocessor may be programmed wirelessly from “cloud based”instructions; etc.

In certain aspects, the inhalation delivery devices of the disclosuremay interface with or communicate with one or more computing devices(e.g., a wireless communication device such as a smart device or otherportable wireless device, a server, a personal computer, etc.). In suchembodiments, a user may interface with software or other applications(e.g., an App on a smart phone) to set a desired dose and/or amountlevel. In certain embodiments, a user may set different dose levels,e.g., depending on the time of day (e.g. a low dose at work and a higherdose in the evening or on weekends). Further, a user may set differentdose and/or amount levels for different agents and/or ingredients. Inyet other embodiments, preset dose limits may be programed into thedevice, e.g., into the controller, the ejector mechanism, thereservoir/ampoule, etc., such that the device may only dispense acertain number of doses per hour, per day, per month, etc. Such afeature may provide for tamper and/or abuse deterrent measures.

The foregoing and other aspects of the present disclosure will bediscussed in further detail with reference made to the figures. FIG. 1is a block diagram illustrating an example inhalation delivery system100 in accordance with one implementation of the present disclosure.However, the embodiment illustrated in FIG. 1 is for illustrativepurposes only, and does not limit the scope of the disclosure. Forinstance, the inhalation delivery device may comprise the dosage andtopography management system, and may include various user interfaces(embodiment not shown).

In general, the system 100 includes a user computing device 122 thatincludes a dosage and topography management system 102 and an optionaltranslation layer 122. The dosage and topography management system 102facilitates retrieval of usage, dosage and device metrics, and otheruser information from one or more interfaced inhalation delivery devices104, stores the retrieved data and information, determines inhalationdelivery device 104 operating parameters, generates instructions foractivation and operation of the inhalation delivery device 104, andgenerates and presents dosage control, usage and inhalation topographydata, and associated information to users, such as through a userinterface, website or other application API 124. The dosage andtopography management system 102 may also provide data and instructionsback to the inhalation delivery device 104 in response to input from theuser via API 124 of computing device 122.

The dosage and topography management system 102 may be implemented invarious ways, but may generally include software modules includingprogramming instructions and code, executable via one or more processorsof user computing device 122.

Data and information may be obtained by the dosage and topographymanagement system 102 from and provided to one or more inhalationdelivery devices 104. In general, the inhalation delivery device 104 maytake various forms and communicate to the dosage and topographymanagement system in various manners, e.g., Bluetooth, wifi, cellular,etc. But, in general, the inhalation delivery device 104 communicateswith the user computing device to provide user data and user informationto the dosage and topography management system 102, and the dosage andtopography management system 102 can provide data and instructions backto the inhalation delivery device 104 in response to input from theusers via user computing device 122. Any suitable wireless communicationmanner, e.g., a wireless communication chip/transceiver, Bluetooth chip,wifi chip, cellular chip, etc., may be used.

As data may be collected in various formats and using various protocols,certain implementations of the present disclosure may include anoptional translation layer 112 configured to facilitate communicationbetween the inhalation delivery device 104 and the dosage and topographymanagement system 102 of the user computing device 122. In certainimplementations, the translation layer 112 may include one or moresoftware modules configured to communicate and receive data from one ormore of the inhalation delivery device 104, and to convert the receiveddata into a standardized format for storage and use by the dosage andtopography management system 102. In certain implementations, thetranslation layer 112 may be implemented using a representational statetransfer (REST)-based architecture. In other implementations, thetranslation layer 112 may instead be implemented using one or moreremote procedure calls (RPC), web services (such as SOAP or WSDL), orother approaches for facilitating communication between computingdevices and/or software modules.

The dosage and topography management system 102 may include, becommunicatively coupled or otherwise have access to one or moredatabases or similar data stores. Such data stores are generally used tostore information for use by the dosage and topography management system102. For example, the system 100 includes each of a user informationdata store 114, an inhalation flow/dosage relationship data store 116, aphysical properties data store 118, and a cessation of use platform datastore 120.

The user information data store 114 may be populated with informationregarding users of the system 100. Such information may include, withoutlimitation, login credentials for users of the system and contactinformation. Information contained within the user information datastore 114 may vary depending on whether the stored data corresponds to alaboratory or clinical user or a patient. The inhalation flow/dosagerelationship data store 116 may include one or more linear or non-linearrelationships between inhalation flow rate and dosage rate based onreadings from internal device sensors to provide, e.g., duration ofdose, etc. Similarly, the physical properties data store 118 may providephysical properties of compositions to assist with calculations of dosesadministered, doses remaining, concentrations, etc. The cessation of useplatform data store 120 may provide preferred dosing regimens fordesired cessation of use profile requests and/or content related tocessation of use. Such content may include text, images, videos, audio,or any other similar content that may be used to convey educational orother information to the user.

Although illustrated in FIG. 1 as distinct data objects, the data stores114-120 may be implemented as more or fewer data objects and, as aresult, the implementation illustrated in FIG. 1 is intended merely as anon-limiting example. For example, more or fewer data sources may beused to store data for use by the dosage and topography managementsystem 102, and particular types of data may be stored or otherwisedistributed across any number of data sources. In certainimplementations, multiple data stores may be used to store the same datato provide redundancy, improved accessibility, or similar benefits.Moreover, while user information, data stores, and content are providedas specific examples of data that may be stored and accessible by thedosage and topography management system 102, it should be appreciatedthat other implementations of the present disclosure may include thestorage, maintenance, and retrieval of other data that may be beneficialto users of the system 100.

It should also be appreciated that the data stores 114-120 are merelyexamples of databases or other data objects that may be used toimplement the system 102. For example, in addition to the user, data andcontent discussed above, additional data objects may be implemented tofacilitate other functions of the system. In other embodiments, fewersources of data may be utilized.

As previously noted, the user computing device 122 may be any of anumber of computing devices including, without limitation, a smartphone,a tablet, a smartwatch, a laptop computer, a desktop computer, or anyother similar computing device. In certain implementations, the useraccesses the dosage and topography management system 102 through anapplication, browser, or similar software executed on the computingdevice 122 and, in some instances, may be a mobile device that providesfast and easy access to the inhalation delivery device 104.

In certain aspects, the inhalation delivery device 104 includes aprocessor 106 which may be programmed to ensure timing and actuation ofthe ejector mechanism in accordance with desired parameters, e.g., basedon the duration of piezoelectric activation to achieve desired dosagesand/or amounts, etc. Processor 106 may be programmed at the factory, orit may receive instructions from user input via the inhalation controldevice 104 or the user computing device 122, as described herein. Dosecounting and lockouts may also be preprogramed into the microprocessoror provided by user instructions from the inhalation delivery device oruser computing device.

In certain embodiments, the inhalation delivery device 104 includes orinterfaces with a memory 108 to record the date-time of each ejectionevent, as well as the user's inhalation flow rate during the doseinhalation to facilitate user monitoring, as well as reservoir usagemonitoring. Although illustrated in FIG. 1 as being onboard theinhalation delivery device 104, inhalation delivery device 104 mayalternatively communicate with a remote memory store, e.g., locatedwithin the user computing device (not shown).

Communication between the dosage and topography management system 102and the user computing device 122 may be facilitate through one or moreapplication programming interfaces (APIs) 124. In one exampleimplementation, such APIs may rely on JavaScript Object Notation (JSON)or a similar standard to for transmission of data between the dosage andtopography management system 102 and the user computing device 122,however, it should be appreciated that communication between the dosageand topography management system 102 and the user computing device 122may occur using any of a number of communication protocols currentlyknown or hereafter developed.

The API 124 may support a variety of functions to facilitate interactionbetween the dosage and topography management system 102, the inhalationdelivery device 104, and the user computing device 122. The followingexamples are merely illustrative of functions and subroutines that maybe included in the API 124 and should not be seen as limiting.

In one aspect, a user may log into the dosage and topography managementsystem 102 by providing appropriate credentials, which may include oneor more of a user name, a password, a multi-factor authentication code,biometric information (e.g., a face scan or fingerprint), or any othersimilar identifying information.

User authentication may also include authentication via the inhalationdelivery device 104. In this regard, the inhalation delivery device 104may include various biometric security components, e.g., fingerprintscanner, in connection with activation, lock/unlock, and interactionwith the dosage and topography management system 102 to furtherauthenticate user credentials. In certain embodiments, an inhalationdelivery device 104 may be paired to one or more user computing devices122 via the dosage and topography management system 102. For example, ainhalation delivery device 102 may be initialized and/or activated by auser via various biometric information (e.g., fingerprint). Uponinitialization, the inhalation delivery device 104 may communicate witha user computing device 122 via a wireless communication network (e.g.,Bluetooth, wifi, cellular, etc.) to pair with an application on the usercomputing device 122. Once paired, the dosage and topography managementsystem 102 can facilitate further interactions between the inhalationdelivery device 104 and the user computing device 122.

API 124 may be used to facilitate user authentication. Such an aspectmay include functionality for authorizing a user, such as by verifyinglogin and password information provided by the user. The API 124 mayfurther support registration and pre-registration of a user, the latterincluding transmission and verification of an authorization number orsimilar verification token that may be transmitted to a user by textmessage, phone, or other communication method.

In other aspects, the disclosure relates to a methods, devices andsystems which facilitate controlled dose and/or amount metering, e.g.,to achieve desired inhalation topography for various compositions of thedisclosure, such as cannabinoid compositions including THC and/or CBD,or nicotine compositions.

In other embodiments of the disclosure, a user may fine tune adose/amount level based upon self-monitoring of their own internal stateor perceptions to achieve a desired inhalation topography and/ortherapeutic window. In certain embodiments, the dose/amount adjustmentsmay include total dosage limits to aid in controlled cessation efforts.For example, total dosage limits per unit time may be set to allow forcontrolled, stepped-down total dosages while maintaining dose meteringto thereby achieve desired dosage levels below the total dosage limits.

Without intending to be limited by theory, in certain aspects of thedisclosure, there is a targeted window for effective dosing of agents ofthe disclosure such as cannabinoid including THC and/or CBD. Forinstance, too little of an amount does not provide effective painrelief, and too much may cause unwanted psychotropic effects or maycause the patient to feel unwell. Likewise, with nicotine dosing, thereis often a targeted window of desired dosing of a user to providedesired outcomes with minimal side effects, particularly duringcessation efforts. Like many pharmaceuticals, effective administrationmay require a larger, initial bolus dose to establish a desired bloodlevel, followed by subsequent smaller doses to maintain the desiredlevel in the blood. The methods, devices and systems of the disclosureallow for controlled dose and/or amount metering to achieve a targetedwindow of administration.

With such agents, effective dosing is often most accurately monitoredand regulated by the patient's own perception and experience. Forinstance, this may be demonstrated by regular users who first take oneor more long, deep inhalations typically followed by shorter, slowerinhalations to reach a satisfactory dosage level. The shorter and slowerinhalations result in a smaller amount of substance reaching the user.

API 124 may further facilitate advanced functionality of the inhalationdelivery device 104. For example, as illustrated in FIG. 2A, API 124 mayprovide a user interface to easily adjust and select independentlycontrolled and metered active agent (e.g., nicotine) and flavor levels.The dosage and amount levels may be selected in any suitable manner,e.g., by increment (a designated selection of 10 increments, adesignated selection of 20 increments, a designated selection of 40increments, a designated selection of 50 increments, etc.), a designatedconcentration of agent/ingredient, a designated weight ofagent/ingredient, etc. Based on input to API 124 regarding the requesteddosage and/or amount levels, dosage and topography management system 102may then interface with inhalation delivery device 104 and provideinstructions to inhalation delivery device 104 to adjust delivery of thecomposition(s) accordingly. Alternatively, the inhalation deliverydevice 104 may include a dosage/amount adjustment interface to controldose and/or amount metering directly from the inhalation delivery device104. Such an interface may include, e.g., toggle buttons, an LCDtouchscreen, voice recognition, or any other suitable mechanism known inthe art.

API 124 may provide yet additional advanced user interface andfunctionality to facilitate dose and amount metering. For example, withreference to FIG. 2B, multiple pre-programed and/or customizable usemodes may be provided and selectable by a user. In certain embodiments,such use modes may provide for varied dosage and/or amount meteringtuned to particular environments, uses, times of day, etc. By way ofnon-limiting example, use modes may include: day, social, night,stealth, custom, etc. Each use mode may be configured withdifferentiated agent (e.g., nicotine, THC, CBD, etc.) andadditive/flavor levels. Without intending to be limited, stealth modemay be configured to allow for independent dose/amount adjustment forthe agent (e.g., nicotine, THC, CBD, etc.) and flavor such that noperceivable vape “smoke” or aerosol is generated. Day mode be configuredto provide higher dosage amounts of the agent (e.g., nicotine, THC, CBD,etc.), while night mode may be configured to provide lower dosage amountof the agent—or vice versa. A social mode setting may provide moderatedosage amounts of the agent and moderate amounts of theadditives/flavors, so as to provide a less invasive user and third partyexperience.

For example, with reference to FIG. 3, a flow chart illustrating anexemplary method 300 for controlling the dose and/or amount of acomposition for delivery to the pulmonary system of a user viainhalation is provided.

For purposes of the following example implementation and to providecontext, reference is made to the various system elements of the labresult processing system 100 of FIG. 1. For example, method 300 willgenerally be described as being executed by the dosage and topographymanagement system 102, the user computing device 122, and/or theinhalation delivery device 104, and of FIG. 1. It should be appreciated,however, that any reference to elements of FIG. 1 should be regarded asexamples only and implementations of the present disclosure are notnecessarily limited to the specific elements, architecture, etc. of thesystem 100 of FIG. 1.

By way of example, with reference to FIG. 3, method 300 relates to amethod for controlling the dose and/or amount of a composition fordelivery to the pulmonary system of a user via inhalation, from theperspective of computing system. In certain embodiments, the computingsystem may comprise the user computing device 122 and/or the inhalationdevice 104. In a first step, a request for a desired dose or amount ofat least one agent or ingredient of a composition for delivery to thepulmonary system of a user via inhalation is received, at a computingsystem, e.g., user computing device 122 and/or an inhalation deliverydevice 104, based on user input (operation 302). The user input may bereceived via a user interface, e.g., API 124, or based on user action,e.g., input from inhalation flow rates during use.

In certain embodiments, the request for a desired dose or amount of atleast one agent or ingredient of a composition may be received at theinhalation delivery device 104, as described herein. In suchembodiments, the request may be transmitted from the inhalation deliverydevice 104 to the user computing device 122 for processing. In otherembodiments, the inhalation delivery device may have preset, executableinstructions for certain dosage requests, and may be to adjust and meterdosing without communication or interaction with the user computingdevice 122.

In other embodiments, rather than using controls via API 124 or theinhalation delivery device 104, a user may regulate dosing and amountmetering by controlling inhalation flow velocity during use, which inturn regulates the total amount delivered via controlling the rate andduration of activation of the ejector mechanism of the device. Such finedosage adjustments may be used to provide desired dose monitoring andinhalation topography, including, e.g., controlled cessation of use.

In response to receiving the request, the computing system determines,e.g., via dosage and topography management system 102, inhalationdelivery device 104 operating parameters to provide the requesteddesired dose or amount of at least one agent or ingredient of acomposition for delivery to the pulmonary system of a user viainhalation (operation 304). Such operating parameters may be anysuitable inhalation delivery device operating parameters to achieve thedesired dosage/amount. In certain embodiments, as described herein,operating parameters may include the duration of activation of apiezoelectric actuator of the inhalation delivery device. Suitableactivation times may be determined, e.g., based of ejection time/dosagecurves and related physical data that may be stored in the memory ofdosage and topography management system 102.

The computing system then generates computer executable instructions foractivation and operation of the inhalation delivery device 104 toprovide the requested desired dose or amount based on the determinedinhalation delivery device operating parameters (operation 306), and thecomputer executable instructions are transmitted to an ejector mechanismof the inhalation delivery device 104 (operation 308) for execution atthe inhalation delivery device to provide for activation and operationof the inhalation delivery device upon use to thereby control the doseand/or amount of the at least one agent or ingredient of a compositionfor delivery to the pulmonary system of user via inhalation.

As described herein, in certain embodiment, methods, devices and systemsare provided which allow for “hands free” dosing/amount metering. Incertain embodiments, a user does not need to select a dosage amount on auser computing device or via buttons or a user interface on theinhalation delivery device. Instead, dose/amount metering may becontrolled by the user according to the duration and/or intensity ofinhalation flow. In certain embodiments, control of dose/amount meteringbased on the length and/or intensity of inhalation flow rate may beaccomplished by monitoring inhalation flow via a pressure or flow sensorin the inhalation delivery device.

In some embodiments, inhalation topography, including maximumdosage/amount or the relationship between inhalation flow rate andduration can be defined, set or modified via the user computing deviceor inhalation delivery device in a similar manner to that describedabove with respect to dose/amount control. By way of non-limitingexample, various zero order, linear, non-linear, step-wise, and otherknown relationships between inhalation flow rate and dosage may beuploaded to the inhalation delivery device, e.g., via the API of theuser computing device. These relationships can then be used by theinhalation delivery device to adjust dose/amount metering based oninhalation flow rates.

FIGS. 4A-4G illustrate exemplary inhalation topography relationshipsbetween inhalation flow rate and composition dispense rate (dose/amountmetering). For example, with reference to FIG. 4A, a linear relationshipis illustrated showing, e.g., an inhalation rate is 60 SLM (Standardliters per minute) dispensing a maximum dispense rate, e.g., 10 uL persecond. At inhalation rates the dosage rate may decrease in a linear.For example, at 30 SLM the dosing rate may be 4 uL per second. As shownin FIG. 4A, at a very small inhalation flow rate, the dosing rate cancut off so that an inhalation flow rate less than, e.g., 10 SLM thecomposition dispense rate would be 0. Thus when a user wants a lowerdosage, they can simply reduce the rate and/or duration of theirinhalation. An additional benefit to a system that ceases dropletdispense when inhalation rates drop below a minimum level is theprevention of waste when a user only wants a very small dose and takesonly a short inhalation.

Examples of alternative relationships between inhalation flow rate anddispense rate are shown in FIGS. 4B-4G. By way of example, FIG. 4Billustrates a non-linear relationship which encourages the user toinhale more slowly to allow better deposition in the lung. To encourageslower inhalation, the maximum droplet dispense rate may be set tosaturate at a preset optimal flow rate for droplet deposition in thelung. For inhalation flow rates above or below an optimal band of flowrates, dosages might be less (or more), to “train” the user to theoptimal flow rate. Such training could be supported by lights or voicemessages from the inhalation delivery device or user computing device,instructing and supplying feedback to the user.

FIGS. 4C, 4D, 4E, 4F, and 4G each illustrate various relationshipsbetween inhalation flow rate and agent dispense rate. FIG. 4C shows asimple relationship wherein dosing is not initiated until a minimumthreshold inhalation flow rate is achieved, and then dosing is initiatedat a preset minimum dose rate. FIG. 4D shows a similar relationship,however the relationship includes a preset maximum dose rate. FIGS. 4Eand 4F illustrate non-linear relationships with preset minimum andmaximum dose rates, with FIG. 4E showing a relationship that providesmore quickly escalating dosing with increased inhalation flow rates andFIG. 4F showing more slowly escalating dosing with increased inhalationflow rates. FIG. 4G illustrates a step wise increasing relationship witha preset maximum dose rate.

In certain embodiments, dispense rate may be controlled by placingmicro-stops (non-active ejection times) in a continuous dispense. Atflows below a preset level (10 SLM in this case), no ejection willoccur. As shown in FIGS. 5A and 5B, by turning the ejector on and off inshort time intervals, an average dispense rate less than the maximumdispense rate may be achieved—in a manner similar to Pulse WidthModulation used to control electrical actuators. To achieve the ejectionrates described, the high frequency driving of a piezo actuator may beturned on and off according to the defined output pattern. For example,an ejector plate that dispenses at a continuous rate of 10 uL per second(microliters per second) can have a dispense rate of 5 uL per second byejecting for 0.01 second and then pausing for 0.01 second. FIGS. 4A and4B illustrate activation sequences to achieve 3 uL (30% dispense rate)and 8 uL (80% dispense rate). Ejection systems such as piezo-drivenmeshes where driving signals are typically about 100 kHz can easilyaccomplish this form of dispense control. Because a piezo systemtypically is driven at resonance and may require 10 to 100 cycles toreach full resonance, it some embodiments, the microprocessor may beprogrammed to provide error correction for any lack of ejection at thestart of micro dispenses.

In some cases, a user may want a dispense duration that is fixed topermit the final part of their inhalation, after dispense has stopped totransport the composition into the lung. For example, dispense durationmay be limited to 1 second so that a 2 second inhalation will transportthe entire bolus to the lungs. In such a case, substance dispense wouldcease at one second, or when inhalation flow rate drops below a presetlevel.

Without intending to be limited, due to the ability to sense userinhalation flow rates and adjust or activate dose/amount metering basedon inhalation rates, the methods, devices and systems of the disclosurehave additional benefits including, e.g., allowing a user to controldosage and/or amount metering; avoiding waste from dispensing while auser is no longer effectively inhaling; allowing user adjustment orpresetting of dispense rates to fit inhalation patterns or preferences;preventing second-hand “smoke” due to a device continuing to dispensedroplets into room air without the user inhaling; avoiding the need forthe user to time a dispense with their inhalations; preventingunauthorized user access (e.g., a child) by requiring a minimuminhalation rate before starting any ejection (e.g., small children arenot able achieve the required inhalation flow rates to activatedispense).

API 124 may also provide additional functionality to a user, e.g., byproviding notifications and information regarding battery life,reservoir fill status, dose counts and use levels (e.g., cigaretteequivalent of nicotine consumed), etc. In other aspects, a user mayaccess historical usage reports through the user interface. Results maybe arranged, for example, in reverse chronological order and the usermay click or otherwise select any of the listed results to “drill-down”and receive additional data and information.

In accordance with certain aspects of the disclosure, the systems of thedisclosure provide a reliable monitoring system that can date and timestamp actual delivery of compositions, including doses and amountsdelivered, e.g., to benefit users through self-monitoring or throughinvolvement of care givers and family members. As described in furtherdetail herein, the inhalation delivery device of the disclosure maydetect inspiratory airflow and record/store inspiratory airflow in amemory (on the inhalation delivery device and/or a user computingdevice). The number of times that delivery is triggered may beincorporated and displayed via a dose counter on the inhalation deliverydevice and/or the API 124 of the user computing device 122.

In some embodiments, the inhalation delivery device and/or the usercomputing device, e.g., via the processor and memory, can monitor dosesadministered and doses remaining in a particular reservoir. In certainembodiments, the reservoir may comprise components that includeidentifiable information, and the inhalation delivery device maycomprise components that may “read” the identifiable information tosense when a reservoir is inserted into the inhalation delivery device,e.g., based on a unique electrical resistance of each individualampoule, an RFID chip, or other readable microchip (e.g.,cryptoauthentication microchip).

In yet other aspects of the disclosure, the methods, devices and systemsinclude:

Personal Identification for Activation—

methods, devices and systems of the disclosure can also include personalidentification keys to prevent unauthorized activation of the device,and delivery of the composition to someone other than the intended user.In certain embodiments, the personal identification key could include,e.g., activation in only specified locations identified via onboard GPS;authentication via PM, blockchain PM or similar public keyauthentication methodologies; biometric authentication, e.g., viaonboard fingerprint recognition or facial recognition; tethering to usercomputing device (e.g., smartphone or smartdevice) with biometricauthentication, e.g., fingerprint or facial recognition, such that theuser computing device sends an activation signal to the inhalationdelivery device upon user authentication.

Authentication Based Lock-Outs—

methods, devices and systems of the disclosure include the ability todeliver a composition with a pre-determined “lock-out” setting based on,e.g., dosage amount, dosing regimen, expiration date, or otherinformation indicative of tampering, misuse or overuse, which “lock-out”setting renders the associated reservoir and/or device inactive orinoperative, either on a permanent basis or temporarily until a pre-setamount of time has passed (e.g., to prevent overdose). In certainembodiments, the reservoir may be configured as a smart ampoule toinclude a readable chip, processor with memory, or other suitablemechanism to allow identification/activation information to beincorporated into a user specific smart ampoule such that the ampoule isidentifiable to the lock-out settings.

Tamper Resistance—

methods, devices and systems of the disclosure also includetamper-resistant reservoirs, configured to reduce tampering and misuseof the compositions housed within the reservoir and tampering or misuseof the physical ampoule itself. In certain embodiments, the reservoirmay be configured such that, if punctured or opened, the compositionhoused within the reservoir is rendered useless by abuse deterrentagents, e.g., polymers, gelling agents, and/or antagonist, etc.,integrated into the structure of the reservoir. In other embodiments,the inhalation delivery devices and/or reservoirs may be configured todetect physical tampering of the reservoir, chemical or physicaltampering of the composition, and/or a combination thereof. If suchtampering is detected, the reservoir, inhalation delivery device, and/oruser computing device may render the composition housed within thereservoir useless and/or deactivate the inhalation deliverydevice—either permanently or temporarily until a non-tampered reservoiris detected.

Cessation of Use—

methods, devices and systems of the disclosure provide for controlledcessation of use and related methods of monitoring to facilitatecessation of use. In certain embodiments, a desired dosage or amount ofdelivery may be achieved via controlled dosage or amount metering. Thedosage or amount may be gradually reduced at predetermined intervals andby predetermined amounts based, e.g., on user input so as to achieve anoverall reduction or cessation of use. By way of non-limiting example,the dosage or amount may be gradually reduced in stepwise manner over aset number of days, weeks or months, e.g., 5%, 10%, 25%, 50%, 75%reduction of dose per actuation, per day, per week, per month, etc.,again, based on user input and desired timeframes for overall reductionor cessation of use. In other aspects, controlled dosage or amountmetering may be adjusted at predetermined time intervals and amounts toas to provide increased amounts during times of increased “usestressors” (e.g., in the morning, at work, during commute time), withreduced doses and amounts at other times. Such adjustments may be usedalone or in combination with gradual reductions in dose/amount, so as toprovide an overall reduction in use. The methods devices and systems mayalso provide user monitoring features to facilitate cessation of use,e.g., monitoring and display of device usage and metrics information.

For example, with reference to FIG. 6, a flow chart illustrating anexemplary method 600 for displaying device usage and metrics informationto a user, e.g., to assist in cessation of use efforts is provided.

For purposes of the following example implementation and to providecontext, reference is made to the various system elements of the labresult processing system 100 of FIG. 1. For example, method 600 willgenerally be described as being executed by the inhalation deliverydevice 104, the user computing device 122, and the dosage and topographymanagement system 102 of FIG. 1. It should be appreciated, however, thatany reference to elements of FIG. 1 should be regarded as examples onlyand implementations of the present disclosure are not necessarilylimited to the specific elements, architecture, etc. of the system 100of FIG. 1.

More specifically, the method 600 generally includes the steps forrequesting and presenting inhalation delivery device usage data,including dosage and amount information. The method 600 may be executed,for example, by a server or similar central computing system (e.g., thedosage and topography management system 102 of FIG. 1) to generatecharts for display on a user computing device (e.g., the user computingdevice 122 of FIG. 1). Method 600 may further include additional stepsdirected to the request and provision of reporting and/or educationalcontent that extend beyond steps directed to generating and displayinghistorical data.

Beginning at operation 602, the user computing device 122 receives aselection of a device usage/metric report from a user. For example, theuser computing device 122 may execute an application (or “app”),program, website, or other software that presents a user interface to auser of the user computing device 122.

In at least certain implementations, the user interface may present auser with a list of available report types, e.g., doses administeredover last 24 hours, last 7 days, last 30 days, last 60 days, etc.;charting of changes in dosing over last 7 days, last 10 days, last 30days, last 60 days, etc., charting of average inhalation topographyprofile over last 7 days, last 10 days, last 30 days, last 60 days, etc.In such implementations, receiving a selection at the user computingdevice 122 may be the result of the user selecting one of the displayedreport types (e.g., by tapping or clicking one of the displayed reporttypes). In other implementations, selecting a report type may includenavigating to a page or similar portion of the user interface configuredto display report results for available report types.

Regardless of how a selection is made, the user computing device 122then generates and transmits a corresponding request for historical datato the dosage and topography management system 102 (operation 604) andor inhalation delivery device 104, depending on the location of thestored data.

The request received by the dosage and topography management system 102and/or inhalation delivery device 104 may include, among other things,one or more of an identifier of the user in question and an identifiercorresponding to the particular report type for which results are to beretrieved. In response to receiving the request and based on thecontents of the request, the dosage and topography management system 102and/or inhalation delivery device 104 retrieves the relevant historicaldata corresponding to the request (operation 506). If the data islocated in the memory of the inhalation delivery device, the data istransmitted back to, and received by the dosage and topographymanagement system 102 (not shown).

The dosage and topography management system 102 may also retrieve charttemplate data associated with the report type and generate the graphicaldata for generating the requested report (operation 608) for use ingenerating a graphical representation of the historical test resultdata. In general, chart templates include various values and parametersfor related to the overall layout and style of a chart associated withthe test type. For example and without limitation, such values andparameters may correspond to margins of the chart and the size,placement, color, and content of various textual or graphical elementsof a chart associated with the test type. The chart template may furtherspecify the total range of displayable values for the chart and a chartsubrange corresponding to a portion of the total range. In at leastcertain implementations, the total range may generally correspond to thevisually displayed range of the vertical axis of the chart while thechart subrange corresponds to a portion of the vertical axis.

In response, the user computing device 122 then renders and displays thegraphical data to display the chart (operation 610). Subsequent torendering and displaying the chart, the user computing device 122 mayreceive another selection corresponding to a graphical element of thechart displayed to the user (operation 612). In response, the usercomputing device 122 may generate and transmit an element selectionmessage to the dosage and topography management system 102 (operation614) requesting additional data and/or educational content. As discussedabove and by way of non-limiting example only, the additional data mayinclude more detailed usage and/or dosage data, educational contentrelevant to cessation efforts, etc. Accordingly, in response totransmitting the element selection message, the user computing device122 receives and displays the additional data or curated content(operation 616).

FIG. 7 is a block diagram illustrating an example of a user computingdevice or computer system 700 which may be used in implementing theembodiments of the components of the system disclosed above. The usercomputing device or computer system (system) includes one or moreprocessors 702-706. Processors 702-706 may include one or more internallevels of cache (not shown) and a bus controller or bus interface unitto direct interaction with the processor bus 712. Processor bus 712,also known as the host bus or the front side bus, may be used to couplethe processors 702-706 with the system interface 714. System interface714 may be connected to the processor bus 712 to interface othercomponents of the system 700 with the processor bus 712. For example,system interface 714 may include a memory controller 718 for interfacinga main memory 716 with the processor bus 712. The main memory 716typically includes one or more memory cards and a control circuit (notshown). In certain embodiments, aspects of the dosage and topographymanagement system described herein may be stored in the main memory 716for execution via one or more processors 702-706. System interface 714may also include an input/output (I/O) interface 720 to interface one ormore I/O bridges or I/O devices with the processor bus 712. One or moreI/O controllers and/or I/O devices may be connected with the I/O bus726, such as I/O controller 728 and I/O device 730, as illustrated. Thesystem interface 714 may further include a bus controller 722 tointeract with processor bus 712 and/or I/O bus 726.

I/O device 730 may also include an input device (not shown), such as analphanumeric input device, including alphanumeric and other keys forcommunicating information and/or command selections to the processors702-706. Another type of user input device includes cursor control, suchas a mouse, a trackball, or cursor direction keys for communicatingdirection information and command selections to the processors 702-706and for controlling cursor movement on the display device.

System 700 may include a dynamic storage device, referred to as mainmemory 716, or a random access memory (RAM) or other computer-readabledevices coupled to the processor bus 712 for storing information andinstructions to be executed by the processors 702-706. Main memory 716also may be used for storing temporary variables or other intermediateinformation during execution of instructions by the processors 702-706.System 700 may include a read only memory (ROM) and/or other staticstorage device coupled to the processor bus 712 for storing staticinformation and instructions for the processors 702-706. The system setforth in FIG. 7 is but one possible example of a computer system thatmay employ or be configured in accordance with aspects of the presentdisclosure.

According to one embodiment, the above techniques may be performed bycomputer system 700 in response to processor 704 executing one or moresequences of one or more instructions contained in main memory 716(e.g., instructions related to the dosage and topography managementsystem). These instructions may be read into main memory 716 fromanother machine-readable medium, such as a storage device. Execution ofthe sequences of instructions contained in main memory 716 may causeprocessors 702-706 to perform the process steps described herein. Inalternative embodiments, circuitry may be used in place of or incombination with the software instructions. Thus, embodiments of thepresent disclosure may include both hardware and software components.

A machine readable medium includes any mechanism for storing ortransmitting information in a form (e.g., software, processingapplication) readable by a machine (e.g., a computer). Such media maytake the form of, but is not limited to, non-volatile media and volatilemedia. Non-volatile media includes optical or magnetic disks. Volatilemedia includes dynamic memory, such as main memory 716. Common forms ofmachine-readable medium may include, but is not limited to, magneticstorage medium; optical storage medium (e.g., CD-ROM); magneto-opticalstorage medium; read only memory (ROM); random access memory (RAM);erasable programmable memory (e.g., EPROM and EEPROM); flash memory; orother types of medium suitable for storing electronic instructions.

The methods, devices and systems of the disclosure may be used with anysuitable inhalation delivery device, such as those disclosed in WO2017/192767 A1 and WO 2019/071008 A1, both of which are hereinincorporated by reference in their entireties. By way of non-limitingexample, the present methods, devices and systems may be used inconnection with the following inhalation delivery device. However, thedisclosure is not so limited, and any suitable inhalation deliverydevice may be used in combination with various aspects of the presentsystems and methods. In one embodiment, an inhalation delivery device ofthe disclosure generally includes a housing, a mouthpiece, at least onefluid reservoir disposed in, connected to, or in fluid communicationwith the housing and the mouthpiece, and at least one ejector mechanismin fluid communication with the reservoir(s). The device may alsoinclude at least one differential pressure sensor positioned within thehousing configured to electronically breath activate the ejectormechanism(s) upon sensing a pre-determined pressure change within thehousing. The device may further include one or more air inlet flowelements to facilitate non-turbulent flow through at least a portion ofthe interior of the housing. The ejector mechanisms may be configured togenerate a controllable plume of an ejected stream of droplets. Theejected stream of droplets may be generated from compositions including,without limitation, solutions, suspensions or emulsions which haveviscosities and surface tensions in a range capable of droplet formationusing the ejector mechanism. Each ejector mechanism may include apiezoelectric actuator, which is directly or indirectly coupled to anaperture plate having a plurality of openings formed through itsthickness. The piezoelectric actuator is operable to directly orindirectly oscillate the aperture plate at a frequency to therebygenerate an ejected stream of droplets. In certain embodiments, theaperture plate may have a hydrophilic coating on at least the fluidintake surface thereof, and an optional hydrophobic coating on the fluidexit surface thereof.

As shown in further detail herein, the droplet delivery device isconfigured in an orientation in that the housing, its internalcomponents, and various device components (e.g., the mouthpiece, airinlet flow element, etc.) are orientated in a substantially in-line orparallel configuration (e.g., along the airflow path) so as to form asmall, hand-held device.

In certain embodiments, the housing and ejector mechanism are orientedsuch that the exit side of aperture plate is perpendicular to thedirection of airflow and the stream of droplets is ejected in parallelto the direction of airflow. In other embodiments, the housing andejector mechanism are oriented such that the exit side of aperture plateis parallel to the direction of airflow and the stream of droplets isejected substantially perpendicularly to the direction of airflow suchthat the ejected stream of droplets is directed through the housing atan approximate 90 degree change of trajectory prior to expulsion fromthe housing.

In specific embodiments, the ejector mechanism is electronically breathactivated by at least one differential pressure sensor located withinthe housing and/or mouthpiece of the inhalation delivery device uponsensing a pre-determined pressure change within the mouthpiece and/orhousing. In certain embodiments, such a pre-determined pressure changemay be sensed during an inspiration cycle by a user of the device.

The ejector mechanism may be comprised of an aperture plate that isdirectly or indirectly coupled to a piezoelectric actuator. In certainimplementations, the aperture plate may be coupled to an actuator platethat is coupled to the piezoelectric actuator. The aperture plategenerally includes a plurality of openings formed through its thicknessand the piezoelectric actuator directly or indirectly (e.g. via anactuator plate) oscillates the aperture plate, having fluid in contactwith one surface of the aperture plate, at a frequency and voltage togenerate a directed aerosol stream of droplets through the openings ofthe aperture plate into the lungs, as the patient inhales. In otherimplementations where the aperture plate is coupled to the actuatorplate, the actuator plate is oscillated by the piezoelectric oscillatorat a frequency and voltage to generate a directed aerosol stream orplume of aerosol droplets.

Several features of the device allow precise dosing of specific dropletsizes. Droplet size is set, in part, by the diameter of the openings ofthe aperture plate, which may be formed with high accuracy. By way ofexample, the openings in the aperture plate may range in size from about0.7 μm to about 200 μm, about 0.7 μm to about 100 μm, about 0.7 μm toabout 60 μm, about 0.7 μm to about 40 μm, about 0.7 μm to about 20 μm,about 0.7 μm to about 5 μm, about 0.7 μm to about 4.7 μm, about 0.7 μmto about 4 μm, about 0.7 μm to about 3.0 μm, about 0.7 μm to about 2.5μm, about 0.7 μm and about 2.0 μm, about 0.7 μm and about 1.5 μm, about0.7 μm and about 1.0 μm-about 5 μm to about 20 μm, about 5 μm to about10 μm, and combinations thereof. A single aperture plate may includeopenings having diameters of the same average diameter (withinmanufacturing tolerances), or a single aperture plate may have openingshaving diameters of different average diameter. By way of non-limitingexample, the same aperture plate may have openings having an averagediameter between about 0.7 μm to about 5 μm, and openings having anaverage diameter between about 5 μm to about 20 μm. The same device mayalso may multiple ejector mechanisms, and therefore multiple apertureplates, each having their own distance opening size distribution.However, other combinations of opening sizes are envisioned as withinthe scope of the present disclosure.

In other aspects, ejection rate, in droplets per second, is generallyfixed by the frequency of the aperture plate vibration, e.g., 108-kHz,which is actuated by a device microprocessor upon activation of theejection cycle (e.g., upon detection of inhalation by one or morepressure sensors of the device). In certain embodiments, there is lessthan a 50-millisecond lag between the detection of the start ofinhalation and full droplet generation.

In some aspects, the inhalation delivery device further includes one ormore air inlet flow elements positioned in the airflow of the housingand configured to facilitate non-turbulent (i.e., laminar and/ortransitional) airflow through at least a portion of the interior of thehousing, e.g., across the exit side of aperture plate, and to providesufficient airflow to ensure that the ejected stream of droplets flowsthrough the droplet delivery device during use. In some embodiments, theair inlet flow element(s) may be positioned within the mouthpiece and/orat an airflow entrance of the housing. In certain embodiments, one ormore air inlet flow element(s) may be positioned behind the exit side ofthe aperture plate along the direction of airflow, in-line or in frontof the exit side of the aperture plate along the direction of airflow,and/or in the mouthpiece. In certain embodiments, the air inlet flowelement(s) may comprise one or more openings formed there-through, andconfigured to increase or decrease internal pressure resistance withinthe inhalation delivery device during use. For instance, the air inletflow element(s) may comprise an array of one or more openings. Incertain embodiments, the air inlet flow element(s) may comprise one ormore baffles, e.g., wherein the one or more baffles comprise one or moreairflow openings.

In certain embodiments, the inhalation delivery device is comprised of aseparate, combination reservoir and ejector mechanism, wherein theejector mechanism is interfaced with the fluid reservoir (e.g.,reservoir/ejector ampoule), and a handheld base unit (e.g., housing)including a microprocessor and power source (e.g., batteries). Incertain embodiments, the microprocessor controls dose delivery, dosecounting and software designed to monitoring parameters that can betransmitted through blue-tooth technology.

In certain embodiments, the combination reservoir/ejector mechanism(e.g., reservoir/ejector ampoule) that may be replaceable or disposableeither on a periodic basis, e.g., a daily, weekly, monthly, as-needed,etc. basis, as may be suitable for the intended use. The reservoir maybe prefilled or filled at use via a suitable injection or fillmechanism. In certain aspects, such disposable/replaceable, combinationreservoir/ejector mechanism may minimize and prevent buildup of surfacedeposits or surface microbial contamination on the aperture plate, owingto its short in-use time.

In certain embodiments, the mouthpiece may be interfaced with (andoptionally removable and/or replaceable), integrated into, or part ofthe housing. In other embodiments, the mouthpiece may be interfaced with(and optionally removable and/or replaceable), integrated into, or partof the reservoir or combination reservoir/ejector mechanism. Further,the breath activation pressure sensor(s) may be located in themouthpiece and/or the housing.

In certain embodiments, the inhalation delivery device is configured soas to be altitude insensitive. For example, the inhalation deliverydevice is generally insensitive to pressure differentials that may occurwhen the user travels from sea level to sub-sea levels and at highaltitudes, e.g., while traveling in an airplane where pressuredifferentials may be as great as 4 psi. In certain implementations, theinhalation delivery device may include a superhydrophobic filter,optionally in combination with a spiral vapor barrier, which providesfor free exchange of air into and out of the reservoir, while blockingmoisture or fluids from passing into the reservoir, thereby reducing orpreventing fluid leakage or deposition on aperture plate surfaces.

In certain embodiments, the droplet delivery device may be turned on andactivated for use by inserting the reservoir/ejector ampoule into thebase unit, opening the mouthpiece cover, and/or switching an on/offswitch/slide bar, etc. In certain embodiments, visual and/or audioindicators may be used to indicate the status of the device in thisregard, e.g., on, off, stand-by, preparing, etc. By way of example, oneor more LED lights may turn green and/or flash green to indicate thedevice is ready for use. In other embodiments, visual and/or audioindicators may be used to indicate the status of the reservoir/ejectorampoule, including the number of doses taken, the number of dosesremaining, instructions for use, etc. For example, and LED visual screenmay indicate a dose counter numerical display with the number ofremaining doses in the reservoir.

As described in further detail herein, during use as a user inhalesthrough the mouthpiece of the device, a differential pressure sensorwithin the device may detect inspiratory flow, e.g., by measuring thepressure drop across a Venturi plate at the back of the mouthpiece. Whena threshold pressure decline (e.g., 8 SLM) is attained, themicroprocessor may activate the ejector mechanism(s), which in turngenerate an ejected stream of droplets into the airflow of the devicethat the user inhales through the mouthpiece. In certain embodiments,audio and/or visual indicates may be used to indicate that dosing hasbeen initiated, e.g., one or more LEDs may illuminate green. Themicroprocessor then deactivates the ejector at a designated time afterinitiation so as to achieve a desired administration dosage, e.g.,1-1.45 seconds. Alternatively, the microprocessor may activate theejector mechanism(s) until such time as the threshold pressure change isno longer detected within the device (indicating that the user is nolonger applying inspiratory flow through the device). In certainembodiments, the device may provide visual and/or audio indicators toindicate dosing.

Following dosing, the droplet delivery device may turned off anddeactivated in any suitable manner, e.g., by closing a mouthpiece cover,switching an on/off switch/slide bar, timing out from non-use, removingthe reservoir/ejector ampoule, etc. If desired, audio and/or visualindicators may prompt a user to deactivate the device, e.g., by flashingone or more red LED lights, providing voice commands to close themouthpiece cover, etc.

In certain embodiments, the inhalation delivery device may include anejector mechanism closure system that seals the aperture plate when notin use to protect the integrity of the aperture plate and to minimizeand prevent contamination and evaporation of the fluid within thereservoir. For example, in some embodiments, the device may include amouthpiece cover that comprises a rubber plug that is sized and shapedto seal the exit side surface of the aperture plate when the cover isclosed. In other embodiments, the mouthpiece cover may trigger a slideto seal the exit side surface of the aperture plate when the cover isclosed. Other embodiments and configurations are also envisioned, e.g.,manual slides, covers, and plugs, etc. In certain aspects, themicroprocessor may be configured to detect when the ejector mechanismclosure, aperture plate seal, etc. is in place, and may thereafterdeactivate the device.

Other aspects of the device of the disclosure that allow for precisedosing of specific droplet sizes include the production of dropletswithin the respirable range early in the inhalation cycle, therebyminimizing the amount of composition being deposited in the mouth orupper airways at the end of an inhalation. In addition, the design ofthe fluid ampoule allows the aperture plate surface to be wetted andready for ejection without user intervention, thus obviating the needfor shaking and priming. Further, the design of the fluid ampoule ventconfiguration together with the ejector mechanism closure system limitsfluid evaporation from the reservoir to less than 150 μL to 350 μL permonth.

The device may be constructed with materials currently used in FDAcleared devices. Standard manufacturing methods may be employed tominimize extractables.

Any suitable material may be used to form the housing of the dropletdelivery device. In particular embodiment, the material should beselected such that it does not interact with the components of thedevice or the fluid to be ejected (e.g., nicotine, THC, active agent,etc.). For example, polymeric materials suitable for use inpharmaceutical applications may be used including, e.g., gamma radiationcompatible polymer materials such as polystyrene, polysulfone,polyurethane, phenolics, polycarbonate, polyimides, aromatic polyesters(PET, PETG), etc.

The reservoir/ejector ampoule may be constructed of any suitablematerials for the intended composition use. In particular, the fluidcontacting portions may be made from material compatible with thedesired agent(s), e.g., nicotine, THC, active agent, etc. By way ofexample, in certain embodiments, the composition only contacts the innerside of the fluid reservoir and the inner face of the aperture plate andpiezoelectric element. Wires connecting the piezoelectric ejectormechanism to the batteries contained in the base unit may be embedded inthe ampoule shell to avoid contact with the composition. Thepiezoelectric ejector may be attached to the fluid reservoir by aflexible bushing. To the extent the bushing may contact the composition,it may be, e.g., any suitable material known in the art for suchpurposes such as those used in piezoelectric nebulizers.

In certain embodiments, the device mouthpiece may be removable,replaceable and may be cleaned. Similarly, the device housing andampoule can be cleaned by wiping with a moist cloth. In certainembodiments, the mouthpiece may be interfaced with (and optionallyremovable and/or replaceable), integrated into, or part of the housing.In other embodiments, the mouthpiece may be interfaced with (andoptionally removable and/or replaceable), integrated into, or part ofthe reservoir/ejector ampoule.

Again, any suitable material may be used to form the mouthpiece of theinhalation delivery device. In particular embodiment, the materialshould be selected such that it does not negatively interact with thecomponents of the device or the fluid to be ejected (e.g., nicotine,THC, active agent, etc.). For example, polymeric materials suitable foruse in pharmaceutical applications may be used including, e.g., gammaradiation compatible polymer materials such as polystyrene, polysulfone,polyurethane, phenolics, polycarbonate, polyimides, aromatic polyesters(PET, PETG), etc. In certain embodiments, the mouthpiece may beremovable, replaceable and sterilizable. This feature improvessanitation for droplet delivery by providing a mechanism to minimizebuildup of aerosolized compositions within the mouthpiece and byproviding for ease of replacement, disinfection and washing. In oneembodiment, the mouthpiece tube may be formed from sterilizable andtransparent polymer compositions such as polycarbonate, polyethylene orpolypropylene, as discussed herein.

In certain aspects of the disclosure, an electrostatic coating may beapplied to the one or more portions of the housing, e.g., inner surfacesof the housing along the airflow pathway such as the mouthpiece, to aidin reducing deposition of ejected droplets during use due toelectrostatic charge build-up. Alternatively, one or more portions ofthe housing may be formed from a charge-dissipative polymer. Forinstance, conductive fillers are commercially available and may becompounded into the more common polymers used in medical applications,for example, PEEK, polycarbonate, polyolefins (polypropylene orpolyethylene), or styrenes such as polystyrene oracrylic-butadiene-styrene (ABS) copolymers. Alternatively, in certainembodiments, one or more portions of the housing, e.g., inner surfacesof the housing along the airflow pathway such as the mouthpiece, may becoated with anti-microbial coatings, or may be coated with hydrophobiccoatings to aid in reducing deposition of ejected droplets during use.Any suitable coatings known for such purposes may be used, e.g.,polytetrafluoroethylene (Teflon).

Any suitable differential pressure sensor with adequate sensitivity tomeasure pressure changes obtained during standard inhalation cycles maybe used, e.g., ±5 SLM, 10 SLM, 20 SLM, etc. For instance, pressuresensors from Sensirion, Inc., SDP31 or SDP32 (U.S. Pat. No. 7,490,511B2) are particularly well suited for these applications.

Embodiments of the present disclosure include various steps, which aredescribed in this specification. The steps may be performed by hardwarecomponents or may be embodied in machine-executable instructions, whichmay be used to cause a general-purpose or special-purpose processorprogrammed with the instructions to perform the steps. Alternatively,the steps may be performed by a combination of hardware, software,and/or firmware.

The description above includes example systems, methods, techniques,instruction sequences, and/or computer program products that embodytechniques of the present disclosure. However, it is understood that thedescribed disclosure may be practiced without these specific details. Inthe present disclosure, the methods disclosed may be implemented as setsof instructions or software readable by a device. Further, it isunderstood that the specific order or hierarchy of steps in the methodsdisclosed are instances of example approaches. Based upon designpreferences, it is understood that the specific order or hierarchy ofsteps in the method can be rearranged while remaining within thedisclosed subject matter. The accompanying method claims presentelements of the various steps in a sample order, and are not necessarilymeant to be limited to the specific order or hierarchy presented.

While the present disclosure has been described with reference tovarious embodiments, it should be understood that these embodiments areillustrative and that the scope of the disclosure is not limited tothem. Many variations, modifications, additions, and improvements arepossible. More generally, embodiments in accordance with the presentdisclosure have been described in the context of particularimplementations. Functionality may be separated or combined in blocksdifferently in various embodiments of the disclosure or described withdifferent terminology. These and other variations, modifications,additions, and improvements may fall within the scope of the disclosureas defined in the claims that follow.

What is claimed:
 1. A method for controlling the dose and/or amount of acomposition for delivery to the pulmonary system of a user viainhalation, the method comprising: receiving, at a computing systembased on user input, a request for a desired dose or amount of at leastone agent or ingredient of a composition for delivery to the pulmonarysystem of a user via inhalation; at the computing system and in responseto receiving the request, determining inhalation delivery deviceoperating parameters to provide the requested desired dose or amount ofat least one agent or ingredient of a composition for delivery to thepulmonary system of a user via inhalation; generating, at the computingsystem, instructions for activation and operation of an inhalationdelivery device to provide the requested desired dose or amount based onthe determined inhalation delivery device operating parameters; andtransmitting the instructions from the computing system to an ejectormechanism of an inhalation delivery device for execution at theinhalation delivery device to provide for activation and operation ofthe inhalation delivery device upon use to thereby control the doseand/or amount of the at least one agent or ingredient of a compositionfor delivery to the pulmonary system of user via inhalation.
 2. Themethod of claim 1, wherein the request for a desired dose or amountcomprises an inhalation topography to achieve a desired dosing regimen.3. The method of claim 2, wherein the inhalation topography facilitatescessation of use.
 4. The method of claim 2, wherein the inhalationtopography gradually reduces the dose or amount over time to therebyfacilitate cessation of use.
 5. The method of claim 2, wherein theinhalation topography includes an initial bolus dose at an initialloading dose, followed by maintenance doses at reduced dose.
 6. Themethod of claim 1, wherein the request includes independently selecteddoses and/or amounts at least two agents or ingredients such thatinstructions are provided to the inhalation delivery device toindependently control the dose and/or amount of each of said at leasttwo agents or ingredients separately.
 7. The method of claim 1, whereinthe composition comprises nicotine, and the method comprises controllingthe dose or amount of nicotine for delivery to the pulmonary system of auser via inhalation.
 8. The method of claim 8, wherein the compositionfurther comprises a flavoring, and the request includes independentlyselected doses and/or amounts for nicotine and the flavoring such thatinstructions are provided to the inhalation delivery device toindependently control the dose and/or amount of each of nicotine and theflavoring separately.
 9. The method of claim 1, wherein the computingsystem is a user computing device, and the user input is received via auser interface of the user computing device.
 10. The method of claim 1,wherein an inhalation delivery device comprises the computing system,and the user input is received via a user interface of the inhalationdelivery device, via input from user inhalation flowrates, or acombination thereof.
 11. The method of claim 10, wherein the userinterface of the inhalation delivery device comprises user inputbuttons, an LCD touchscreen, or combinations thereof.
 12. A computingsystem comprising: one or more processors; and a memory storinginstructions executable by the one or more processors, wherein, whenexecuted by the one or more processors, the instructions cause the oneor more processors to: receive, based on user input, a request for adesired dose or amount of at least one agent or ingredient of acomposition for delivery to the pulmonary system of a user viainhalation; determine inhalation delivery device operating parameters toprovide the requested desired dose or amount of at least one agent oringredient of a composition for delivery to the pulmonary system of auser via inhalation; generate instructions for activation and operationof an inhalation delivery device to provide the requested desired doseor amount based on the determined inhalation delivery device operatingparameters; and transmit the instructions to an ejector mechanism of aninhalation delivery device for execution at the inhalation deliverydevice to provide for activation and operation of the inhalationdelivery device upon use to thereby control the dose and/or amount ofthe at least one agent or ingredient of a composition for delivery tothe pulmonary system of user via inhalation.
 13. The system of 12,wherein the request for a desired dose or amount comprises an inhalationtopography to achieve a desired dosing regimen.
 14. The system of claim13, wherein the inhalation topography facilitates cessation of use. 15.The system of claim 13, wherein the inhalation topography graduallyreduces the dose or amount over time to thereby facilitate cessation ofuse.
 16. The system of claim 13, wherein the inhalation topographyincludes an initial bolus dose at an initial loading dose, followed bymaintenance doses at reduced dose.
 17. The system of 12, wherein thecomputing system is a user computing device, and the user input isreceived via a user interface of the user computing device.
 18. Thesystem of 12, wherein an inhalation delivery device comprises thecomputing system, and the user input is received via a user interface ofthe inhalation delivery device, via input from user inhalationflowrates, or a combination thereof.
 19. The system of claim 18, whereinthe user interface of the inhalation delivery device comprises userinput buttons, an LCD touchscreen, or combinations thereof.
 20. A methodof displaying historical data of use of an inhalation delivery device,the method comprising: receiving, at a user computing device from a userinterface, a request for historical data associated with use of aninhalation delivery device to deliver an inhaled composition, thehistorical data comprising an element selected from: number of dosesadministered, dosages and amounts administered, average inhalationtopography, and combinations thereof; transmitting, from the usercomputing device to an inhalation delivery device, the request forhistorical data; receiving, at the user computing device from theinhalation delivery device, the requested historical data; generating,at the user computing device, graphical data for rendering anddisplaying a report of the requested historical data; rendering thegraphical data, at the user computing device; and displaying a report ona display of the user computing device, the report including graphicalelements including the historical data.
 21. The method of claim 20,wherein the displaying of historical data of use of an inhalationdelivery device facilities the cessation of use.
 22. The method of claim20, wherein rendering the graphical data further includes displayingchanges in dosage amounts over time to illustrate reductions orincreases in use of the inhalation delivery device.
 23. The method ofclaim 20 further comprising: receiving a selection of a graphicalelement of the report at the user computing device; generating, inresponse to receiving the selection, additional graphical data relatedto the selected graphical element; rendering the additional graphicaldata, at the user computing device; and displaying a report on a displayof the user computing device, the report including additional graphicaldata related to the selected graphical element.
 24. The method of claim23, wherein the report comprises education information related tocessation of use.